Translational toxicology of metal(loid) species: linking their bioinorganic chemistry in the bloodstream to organ damage onset.

Abstract

The quantification of arsenic, mercury, cadmium and lead in the human bloodstream is routinely used today to assess exposure to these toxic metal(loid)s, but the interpretation of the obtained data in terms of their cumulative health relevance remains problematic. Seemingly unrelated to this, epidemiological studies strongly suggest that the simultaneous chronic exposure to these environmental pollutants is associated with the etiology of autism, type 2 diabetes, irritable bowel disease and other diseases. This from a public health point of view undesirable situation urgently requires research initiatives to establish functional connections between human exposure to multiple toxic metal(loid) species and adverse health effects. One way to establish causal exposure-response relationships is a molecular toxicology approach, which requires one to unravel the biomolecular mechanisms that unfold after individual toxic metal(loid)s enter the bloodstream/organ nexus as these interactions ultimately determine which metabolites impinge on target organs and thus provide mechanistic links to diseases of unknown etiology. In an attempt to underscore the importance of the toxicological chemistry of metal(loid)s in the bloodstream, this review summarizes recent progress into relevant bioinorganic processes that are implicated in the etiology of adverse organ-based health effects and possibly diseases. A better understanding of these bioinorganic processes will not only help to improve the regulatory framework to better protect humans from the adverse effects of toxic metal(loid) species, but also represents an important starting point for the development of treatments to ameliorate pollution-induced adverse health effects on human populations, including pregnant women, the fetus and children.